Journal of affective disorders最新文献

Objective: To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression.

Methods: For treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with psychological support. The resulting psychedelic experience (Five-Dimensional Altered States of Consciousness questionnaire [5D-ASC] and Emotional Breakthrough Inventory [EBI]) were measured. These proximal variables and outcome 3 weeks post-administration (change in Montgomery-Åsberg Depression Rating Scale [MADRS]) were explored using correlation analysis.

Results: The mean intensity of psychedelic effects was dose-related, but distributions of scores for different doses overlapped considerably. Depression response correlated with select aspects of the psychedelic experience overall and for individual doses. At the 25 mg dose, 5D-ASC dimensions Oceanic Boundlessness (Pearson correlation coefficient r = -0.508) and Visual Restructuralization (r = -0.516), and EBI (r = -0·637) were the variables with the strongest correlation to the Week 3 change from Baseline in MADRS score.

Limitations: The existence of correlation does not establish causation and exploratory findings require further replication, preferably in larger independent samples.

Conclusions: The intensity of psychedelic experience overlaps widely across doses and mitigates the risk of unblinding to dose. Correlations between psychedelic experience and outcome suggest specificity in psilocybin's mechanism of action. Quality and intensity of psychedelic experience may be a measure of pharmacodynamic effect and reveal an effective dose response phenomenon for single oral doses.

Background: Skeletal muscle mass to visceral fat area ratio (SVR) has emerged as a key indicator for evaluating sarcopenic obesity (SO). The study aimed to elucidate the association between SVR and depression among US adults.

Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018, this cross-sectional study employed weighted multivariable logistic regression and restricted cubic splines (RCS) to explore the association between SVR and depression. Subgroup and interaction analyses were also performed.

Results: The analysis encompassed 7,262 US adults. In the fully adjusted model, a significant negative association between SVR and depression was observed (OR = 0.35, 95%CI: 0.14-0.87). Additionally, SVR was significantly negatively correlated with mild (OR = 0.53, 95 % CI: 0.30-0.96) and severe depression (OR = 0.19, 95 % CI: 0.05-0.84). When SVR was stratified into quartile (Q1-Q4), individuals in the highest quartile exhibited a lower likelihood of depression compared to those in the lowest quartile (OR = 0.65, 95 % CI: 0.42-0.99). Additionally, the third quartile of SVR was significantly negatively associated with mild depression (OR = 0.72, 95 % CI: 0.53-0.98). No significant non-linear dose-response relationship between SVR and depression prevalence was detected (P-nonlinear = 0.3387). The association remained significant in several subgroup analyses. However, the interaction test revealed that none of the stratified variables were significant (all P for interaction > 0.05).

Conclusion: The study was pioneering in establishing a negative association between SVR and depression within the US population.

Background: Extensive research, predominantly in adults, has highlighted structural brain variations among patients with major depressive disorder (MDD). However, emerging adults, who undergo significant cortical reshaping and are highly vulnerable to depression, receive relatively little attention, despite reporting a higher prevalence of childhood trauma experiences. This study examines cortical gyrification and thickness in emerging adults with first-episode, treatment-naïve MDD, with the objective of investigating their association with childhood trauma.

Methods: Eighty-six emerging adults diagnosed with MDD, aged 18 to 25, and eighty-one healthy controls (HCs), underwent T1-MRI scans. We compared the local gyrification index (LGI) and cortical thickness (CT) between the two groups. Subsequently, we examined the relationship between the LGI and CT in clusters showing differences and childhood trauma as well as clinical characteristics in emerging adults with MDD.

Results: Compared to HCs, MDD showed decreased LGI in the bilateral superior frontal cortices (SFC) and CT in the left pericalcarine cortex (PCC), while an increase in CT was observed in the left lateral orbitofrontal cortex (OFC). The reduction in LGI of the right SFC and the decrease in CT of the left PCC are associated with childhood trauma. Notably these brain abnormalities were not significantly associated with depressive and anxiety symptoms, or the duration of illness.

Conclusion: Abnormal cortical development observed in emerging adults with first episode depression may act as a predisposing factor for depression, irrespective of clinical manifestations, and may be linked to childhood trauma.

Background: Suicidal behavior results from a complex interplay between stressful events and vulnerability factors, including cognitive deficits. Poorer performance on the Stroop task, a measure of cognitive control, has been associated with suicidal behavior in numerous studies. The objective was to conduct an updated systematic review of the literature on the Stroop task as a neuropsychological test of vulnerability to suicidal acts in patients with mood and other psychiatric disorders, while also looking at how the type (classic versus emotional) or the version (paper or computerized) of the Stroop task, as well as the characteristics of the patient (clinical population, age, sex) moderated the Stroop effect.

Methods: A search on Medline, Embase, PsycInfo databases, and article references was performed. 53 studies (6781 participants) met the selection criteria. Interference time and errors of the Stroop Test were assessed in at least 3 studies to be analyzed. Moderators, such as the type (classic versus emotional) of the Stroop task and the characteristics of the patient (clinical population, age, sex) were also assessed.

Results: Interference time on Stroop performance was lower in suicide attempters than in patient controls (g = 0.20; 95%CI [0.10-0.30]) and healthy controls (g = 0.79; 95 % CI [0.29-1.29]), with patient controls scoring lower than healthy controls (g = -0.63; 95%CI [-1.01-0.25]). This was moderated by age and having a mood disorder. In terms of interference errors, suicide attempters performed worse than healthy controls (g = 0.57; 95%CI [0.01-1.15]) but did not perform differently from patient controls (g = 0.20; 95 % CI [-0.06-0.45]). Patient controls also did not score differently than healthy controls (g = -0.18; 95 % CI [-0.54-0.18]). There was a significant moderation effect for the type (i.e., original Stroop task) and version (i.e., paper format) of the Stroop task, and for some characteristics of the patient (i.e., older patients and having a mood disorder).

Conclusions: Cognitive control impairment was associated with a history of suicidal behavior in patients, especially in older populations and those with mood disorders, however this result was moderated by outcome measure (interference time vs. errors), the type (i.e., original Stroop task) and the version (i.e., paper format) of the Stroop task. Cognitive control processes may be an important factor of suicidal vulnerability. Choosing the right neurocognitive test in the right population to detect suicide vulnerability is important direction for future research.

Background: Inescapable stress leads to various long-lasting physical and mental dysfunctions. Acute stress exposure is linked to a high risk of psychological disorders, such as anxiety disorders. The medial prefrontal cortex (mPFC) and periaqueductal gray (PAG) are anatomical regions associated with social information processing and emotional valence. However, it is unclear whether mPFC projections to the PAG are involved in anxiety behavior.

Methods: In this study, an anxiety model by an inescapable foot shock was established. And used immunofluorescence, FosTRAP strategy, specific chemogenetics, optogenetics and behavior test to reveal that the stressful event increased the anxiety behavior of mice after exposure to foot shock and activation of mPFC-PAG circuitry can improve anxiety-like behavior and the locomotor behavior of mice.

Results: Notably, FosTRAP results indicated that c-Fos expression in the PAG and mPFC is increased during foot shock, but inhibiting these brain regions did not significantly alleviate anxiety behavior. Additionally, chemogenetic activation of mPFC projections to the PAG improved anxiety-like behavior and locomotor activity in mice only during stress. Optogenetic activation of the mPFC-PAG circuitry increased the total distance traveled in the open field test and slightly increased the number of entries into the center area, while optogenetic inhibition slightly increased anxiety-like behavior in control mice.

Limitation: The limitation of this study is that only the changes and regulations of mPFC-PAG of anxiety male animals were studied.

Conclusions: Overall, our findings suggest that the valence-encoding mPFC-PAG circuit modulates anxiety, and that these projections may be potential targets for treatment of anxiety disorders.

Orexin receptor antagonists are a group of medications primarily developed to treat insomnia. Preliminary studies support their efficacy in the treatment of depression. In this systematic review, we aim to evaluate the efficacy of orexin receptor antagonists for the treatment of major depressive disorder (MDD). Electronic databases were searched from inception to February 2024 to find relevant studies. Original studies in English that evaluated efficacy of orexin receptor antagonists were included. A total of five randomized clinical trials involving 498 participants were included. Seltorexant (20 mg) significantly decreased depression scores when compared to placebo, as measured by the Hamilton Depression Rating Scale (HDRS). In patients with inadequate responses to antidepressants, seltorexant (20 mg) also showed improvement in Montgomery-Ǻsberg Depression Rating Scale (MADRS) total scores compared to placebo. However, filorexant did not exhibit a significant difference in MADRS total scores compared to placebo. A separate study on seltorexant (40 mg) for MDD patients resulted in a non-significant decrease in depressive symptoms compared to placebo, as measured by the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR). Taken together, these findings highlight the potential of orexin receptor antagonists, particularly seltorexant, as a novel avenue for managing depressive symptoms in MDD. Further research is warranted to better understand their role in depression treatment and their safety profile.

Background: The gut microbiome is critical for the pathophysiology of depression, and inflammation is one of the factors contributing to depression. Fzd6 has been implicated in depression. This study aimed to elucidate the effects of the Fzd6 mutation on gut microbiota structure and the possible regulatory mechanisms involved in depression-associated neuroinflammation.

Methods: Wild-type (Fzd6^WT) and Fzd6 mutant (Fzd6^Q152E) male mice were treated with lipopolysaccharide (LPS) for 7 days. Behavioral experiments were used to detect the behavioral changes of mice in each group, and the composition of intestinal flora and systemic inflammation levels of mice were further detected.

Results: In LPS mice, the Fzd6 mutation enhanced depression-like behavior symptoms, increased the release of pro-inflammatory cytokines, decreased the release of anti-inflammatory cytokines, and caused intestinal flora disturbance. Subsequently, 16SrRNA sequencing revealed significant changes in the relative abundance of the inflammation-associated bacterial groups Ruminococcaceae and Lachnospiraceae in Fzd6^Q152E mice. In mice with depression, the levels of G protein-coupled receptors, GPR41 and GPR43, and glucagon-like peptide-1 (GLP-1) in the small intestine were down-regulated, and the expression of GLP-1 receptor (GLP-1R), peroxisome proliferators activated receptors gamma (PPAR-γ), and nuclear factor kappa-B inhibitor alpha (IκBα) in the hippocampus was also down-regulated, while the expression of nuclear factor kappa-B p65 (NF-κB p65) was up-regulated.

Limitations: The size of the spleen was not studied in this model, and the Fzd6 mutation itself does not cause systemic inflammation such as IL-6.

Conclusion: These results demonstrate that mutations in Fzd6 regulate the composition of the gut flora, which contributes to depression-associated inflammation.

Background: Utilisation of health services is low and delayed among individuals with mood mental disorders and anxiety disorders, despite high disease burdens and available effective treatments. This study aims to examine patterns and delays in help-seeking and associated factors among individuals with lifetime disorder of mood disorders and/or anxiety disorders.

Methods: We used data from the China Mental Health Survey (CMHS), a nationally representative multistage clustered-area probability sample study across 31 provinces. We assessed lifetime mental disorders and help-seeking behaviour using the Composite International Diagnostic Interview (CIDI). Logistic regression analyses were used to examine sociodemographic and clinical correlates of delay to seek health care.

Results: Among 32,552 participants, we identified 3075 patients with lifetime mood and/or anxiety disorders; 486 (15.5 % [95 % CI: 13.6-17.5 %]) have sought health care. Of these, 163 (4.8 % [95 % CI: 3.7-6.3]) ever sought specialized mental health services. The delays to initial health care were 1.0 (IQR: 0-7.1), 1.9 (0-10.0), and 10.0 (1.0-22.1) years for depressive, bipolar, and anxiety disorders. Patients with comorbidities, later age of onset, and living in urban areas showed a higher propensity for help-seeking (all p < 0.05). Older cohort was associated with longer delays in seeking health care, while a later age of onset was associated with shorter delays (all p < 0.05).

Limitations: The cross-sectional retrospective design and self-assessment approach may add bias.

Conclusions: Failure and delays in help-seeking are common in China. National strategies are needed to promote health care utilisation.

Background: Youth with depression may be at a higher risk of developing bipolar disorder (BD). Self-reported, dimensional measures, like the Bipolar Spectrum Diagnostic Scale (BSDS), aim to assess for BD in these groups. We explored properties of this instrument within a cohort of depressed, help-seeking youth.

Methods: We used baseline data from two randomized controlled trials for depressed youth (aged 15-25 years) who had no history of BD or psychosis and who completed the BSDS (n = 240; mean Age = 19.9 years, SD = 2.7; Female = 57 %). Structured diagnostic assessments were repeated at 26-weeks to detect new-onset BD. We examined false-positive rates for concurrent BD using established thresholds on the BSDS, utilised factor analyses to determine its underlying structure, and explored associations between the BSDS and demographic, clinical, and personality variables using linear regressions.

Results: False-positives rates were high. Most (60 %) participants scored above BSDS thresholds at baseline, though none developed BD over the 26-week study period. A three-factor model best fit BSDS items, representing depression, mania, and lability factors. BSDS total, mania and lability sub-scale scores were associated with similar characteristics, with a different pattern of association for the BSDS depression subscale.

Limitations: With no long-term follow-up of the current sample nor a separate bipolar youth sample, we were unable to determine the overall discriminant validity, sensitivity, or longer-term predictive validity of the BSDS.

Conclusion: At recommended thresholds, BSDS has high false positive rates for detecting current BD in youth with moderate to severe depression, especially with mental state or personality disorder comorbidities.